Treatments targeted to enhance brain neurotrophic factor signalling could improve memory functions in Alzheimer’s disease even though they don’t alter brain amyloid burden, according to recent research from the University of Eastern Finland. The enhancement of brain derived neurotrophic factor (BDNF) signalling alleviated memory impairment in Alzheimer’s mouse models. In addition, the administration of cerebral dopamine neurotrophic factor (CDNF) into brain tissue improved long-term memory in particular.

Alzheimer’ disease is the most common cause of dementia, characterised by the accumulation of amyloid beta peptide in the brain, and so far without a cure. As treatments aimed at reducing amyloid deposits have proved unsuccessful, other treatment approaches are needed. Brain neurotrophic factors offer one potential approach.

Neurons communicate with each other via synaptic connections. Impaired synaptic activity and synapse loss have been reported in Alzheimer’s disease, and synapse loss has been shown to correlate with the severity of memory impairment. Reduced levels of BDNF, the most important neurotrophic factor affecting synaptic function, have also been linked to Alzheimer’s disease and cognitive impairment in humans. Hence, the researchers considered it worthwhile to investigate how alterations in BDNF signalling affect memory functions and brain pathology.

Using transgenic APP/PS1 mouse models of Alzheimer’s disease with altered BDNF signalling, the research group showed that memory impairment was aggravated by reduced BDNF signalling and alleviated by enhanced BDNF signalling.

Another focus of interest was the potential of CDNF in the treatment of Alzheimer’s disease. CDNF has shown strong neuroprotective and even restorative properties in animal models of Parkinson’s disease as well as spinal and peripheral nerve injuries. However, its therapeutic effect has not been previously studied in Alzheimer’s disease. In this study, CDNF was infused as a pure protein or in a viral vector directly into brain hippocampus. The treatment was shown to improve long-term memory performance of APP/PS1 and wild-type mice.

Both the mice with modifications in BDNF signalling on top of Alzheimer’s transgenes and the APP/PS1 mice treated with CDNF underwent an extensive behavioural test battery to measure neurotrophic factor effects on memory functions. The impact on amyloid deposits was studied histologically.

“None of the neurotrophic factor manipulations influenced amyloid deposition, while they all had effects on memory function, also in wild-type mice without amyloid beta pathology,” says Susanna Kemppainen, MSc, who presented the results in her doctoral thesis.

“Thus, by enhancing neurotrophic factor signalling it may be possible to improve memory functions without altering brain amyloid burden.”

The findings were originally published in Neurobiology of Aging, PLOS ONE and Behavioural Brain Research. Susanna Kemppainen’s doctoral thesis, entitled The role of neurotrophic factors in Alzheimer's disease, special emphasis on brain-derived neurotrophic factor and cerebral dopamine neurotrophic factor, is available for download at http://epublications.uef.fi/pub/urn_isbn_978-952-61-2736-1/urn_isbn_978-952-61-2736-1.pdf.

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The University of Eastern Finland, UEF, is one of the largest universities in Finland. The activities of the UEF underscore multidisciplinarity, and the university is especially strong in research related to forests and the environment, health and well-being, and new technologies and materials.
The UEF offers teaching in more than 100 major subjects. In addition to the high standard of teaching, the university offers its students a modern study environment, which is under constant development.
The university comprises four faculties: the Philosophical Faculty, the Faculty of Science and Forestry, the Faculty of Health Sciences, and the Faculty of Social Sciences and Business Studies. The university’s campuses are located in the heart of beautiful eastern Finland in Joensuu, Kuopio and Savonlinna.
The UEF is home to approximately 15 000 students and nearly 2 800 members of staff.